Strial marginal cells are known to secrete K+ into endolymph via apical IsK/KvLQT1 (IKs) channels. Regulation of K+ secretion by several hormones is important for inner ear homeostasis but the role of vasopressin in the cochlea is still controversial. We examined the effect of arginine vasopressin (AVP) on marginal cells in the middle turn of the neonatal rat cochlea using nystatin-perforated whole-cell recordings at 24 degrees C. Whole-cell capacitance was 27.3 + 1.1 pF (n = 31). AVP(10(-8) M) gradually increased the IKs channel current in 30 min from the basal (1.1 +/- 0.3 pA; n = 6) to the peak level (714.7 +/- 197.5 pA; n = 6). The deactivation curve of the IKs channel current was best fitted to a biexponential function. 1-Deamino-D-arginine vasopressin (DDAVP; 10(-8) M; n = 5) and 8-bromo-cAMP (10(-4) M; n = 5) also mimicked the effect of AVP with similar time courses. However, 10(-9) M AVP (n = 7) and DDAVP (n = 5) showed no response. The majority of the increase in the IKs channel current caused by 10(-8) M AVP, 10(-8) M DDAVP or 10(-4) M cAMP was blocked within 2 min by the application of chromanol 293B (10(-5) M), a selective blocker of the IKs channel. Our results demonstrate that AVP increases the IKs channel current in marginal cells of the neonatal rat at a concentration of 10(-8) M, and the fact that 8-bromo-cAMP (10(-4) M) and DDAVP (10(-8) M) also showed similar effects at 24 degrees C may suggest the involvement of V2 receptors and the subsequent activation of the cAMP signal pathway.